The goal of this proposal is to develop a promising new approach for non-invasive early detection and diagnosis of oral neoplasia based on fluorescence and reflectance spectroscopy and imaging. Oral cancer is a major global health problem. Early detection and diagnosis is the best way to improve survival and reduce morbidity from oral cancer; yet no method currently exists to accomplish this goal. Fluorescence and reflectance spectroscopy can non-invasively probe biochemical and architectural changes in tissue that occur during carcinogenesis, and mathematical models can relate some of these changes, such as increased metabolic activity and angiogenesis, to observe optical spectra. Over the last four years, we have shown that fluorescence and reflectance spectroscopy can non-invasively and objectively discriminate between normal and abnormal oral mucosa with good sensitivity and specificity - similar to that of oral cancer specialists. The goal of this proposal is to leverage these advances to develop, evaluate and optimize an oral cancer screening approach using fluorescence and reflectance spectroscopy in a community setting to facilitate detection and diagnosis of oral lesions. As part of this competitive renewal, we are now poised to integrate the knowledge gained in these studies to achieve four important goals: (1) to translate these research findings to develop a simplified, non-invasive and objective device to be used in the community; (2) to implement real time data analysis software to provide a clinically meaningful diagnosis at the point-of-care; (3) to test the performance of this device to detect oral dysplasia and early carcinoma in various clinical settings and optimize its integration with existing diagnostic methods; and (4) to investigate the ability of optical spectroscopy as a new biomarker of risk of malignant conversion that can be measured in vivo without the need for biopsy. Successful completion of this research program will provide a portable objective device to screen for oral neoplasia that can be implemented in primary care dental and medical environments where oral cancer expertise is limited and screening is most urgently needed. Knowledge gained through this proposal will facilitate optimal integration of new diagnostic technologies to optimize oral cancer screening and surveillance in diverse patient populations. Further, results will show whether detectable optical features can serve as biomarkers to better identify which patients are at high risk to progress to invasive cancer. The use of this approach, if successful, could significantly improve the survival and quality of life of people worldwide who are likely to suffer from oral malignancies